Obesity is generally defined as the excessive accumulation of body fat. A body weight 20% over that in standard height-weight tables is widely accepted as an obese condition (except for certain heavily muscled persons). Since 1985 obesity has been recognized as a chronic disease, and is the second leading cause of preventable death in the United States.
The increasing prevalence of obesity and preobesity, or overweight, is a major public health issue in the United States. Approximately one third of adults are estimated to be obese. According to the U.S. Bureau of the Census, approximately 58 million American adults (26 million men and 32 million women) are obese. Socioepidemiologic studies suggest that age, socioeconomic status, and genetics may be important risk factors. For example, there is a two-fold increase in the prevalence of obesity between the ages of 20 and 55. Obesity is also far more common among black than white women, occurring in about 60% of middle-aged black women (“The Merck Manual of Diagnosis and Therapy”, Berkow et al., 16th Edition, 1992, Merck Research Laboratories).
Obesity has important medical consequences. Studies suggest a relationship between obesity and an increased risk of cardiovascular disease, including coronary heart disease and stroke, and hypertension. Hypertension, or high blood pressure, is the most important risk factor predisposing to stroke and is an important risk factor predisposing to coronary atherosclerosis.
One important system involved in regulating blood pressure is the renin-angiotensin-aldosterone system (RAS). In this system, renin, a proteolytic enzyme formed in the granules of the juxtaglomerular apparatus cells of the kidney, catalyzes the conversion of angiotensinogen (a plasma protein) into angiotensin I, a decapeptide. This inactive product is then hydrolyzed by angiotensin converting enzyme (ACE) to an octapeptide, angiotensin II, which is a potent vasoconstrictor and also stimulates the release of aldosterone. Aldosterone is an adrenal cortex hormone that promotes the retention of salt and water by the kidneys, and thus increases plasma volume, resulting in an increase in blood pressure.
ACE is produced in the endothelium of somatic tissues and in the testis. It is expressed ubiquitously in the vasculature, including highly vascularized organs such as the lung, heart, pancreas, and kidney. ACE, also referred to as peptidyl dipeptidase A (EC 3.4.15.1) and kininase II, is a metallopeptidase, more particularly, a zinc dipeptidase which, in addition to angiotensin I, can also hydrolyze other biologically active polypeptides, such as kinins, e.g., bradykinin. Bradykinin is a vasodilator, which acts, at least in part, by inducing the release of vasodilator prostaglandins, and which is inactivated upon hydrolysis by ACE. Hence, ACE activity regulates blood pressure, at least in part by producing angiotensin II, a vasoconstrictor, and by inactivating bradykinin, a vasodilator.
Given its wide tissue distribution and its broad substrate specificity, ACE plays a pivotal role in the RAS regulation of blood pressure.